The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

The present invention provides a recombinant herpes simplex virus (HSV), comprising (a) a mutation of the glycoprotein B (gB) at position 285 or 549, (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of an HSV gene required for HSV replication, wherein said target sequence is the reverse complement of microRNA miR-124 and wherein said target sequence is present in the ICP4 gene, and (c) a transgene encoding a matrix metalloproteinase. The present invention also provides a method of killing a cancerous cell using a recombinant HSV according to the invention and a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a recombinant HSV according to the invention.

A mutant HSV-1 (referred to herein as KOS-NA) was generated. KOS-NA contains novel mutations in the UL39 gene, which encodes for a protein that is a large subunit of ribonucleotide reductase (i.e., ICP6). These UL39 mutations were found to alter two amino acids in ICP6 (R950H and L393P) and are responsible for attenuation of KOS-NA in vivo, and resulted in diminished ICP6 protein levels. These novel UL39 mutations regulate the expression and/or stability of ICP6 and severely impact HSV-1 pathogenesis. Mutant HSV viruses containing these mutations appear to protect against HSV infection and can serve as therapeutic vaccines to help combat preexisting HSV infection in infected individuals.

Recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such, and methods of use thereof are each provided.

The present disclosure relates to recombinant oncolytic viral vectors for the treatment and prevention of cancers such as glioblastoma. The oncolytic viral vectors comprise one or more of the following features: miRNA target sequence(s) for viral replication restriction; transgene(s) encoding one or more payload molecules; a retargeting domain; mutation(s) in both UL30 and UL23 genes; and a protein with a syncytial mutation and a counterpart protein without the syncytial mutation.

A mutant HSV-1 (referred to herein as KOS-NA) was generated. KOS-NA contains novel mutations in the UL39 gene, which encodes for a protein that is a large subunit of ribonucleotide reductase (i.e., ICP6). These UL39 mutations were found to alter two amino acids in ICP6 (R950H and L393P) and are responsible for attenuation of KOS-NA in vivo, and resulted in diminished ICP6 protein levels. These novel UL39 mutations regulate the expression and/or stability of ICP6 and severely impact HSV-1 pathogenesis. Mutant HSV viruses containing these mutations appear to protect against HSV infection and can serve as therapeutic vaccines to help combat preexisting HSV infection in infected individuals.

The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

The present invention is directed to Herpes simplex-2 viruses that may be used in vaccines to immunize patients against genital herpes.

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.